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Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis.
Title | Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Mei, SHJ, Haitsma, JJ, Santos, CC dos, Deng, Y, Lai, PFH, Slutsky, AS, W Liles, C, Stewart, DJ |
Journal | Am J Respir Crit Care Med |
Volume | 182 |
Issue | 8 |
Pagination | 1047-57 |
Date Published | 2010 Oct 15 |
ISSN | 1535-4970 |
Keywords | Acute Lung Injury, Animals, Anti-Bacterial Agents, Combined Modality Therapy, Female, Gene Expression Regulation, Immunomodulation, Inflammation, Mesenchymal Stem Cell Transplantation, Mice, Mice, Inbred C57BL, Multiple Organ Failure, Sepsis, Survival Analysis |
Abstract | RATIONALE: Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of sepsis-induced multiple organ dysfunction. OBJECTIVES: We hypothesized that mesenchymal stem cells (MSCs), which have been shown to have immunomodulatory properties, would reduce sepsis-induced inflammation and improve survival in a polymicrobial model of sepsis. METHODS: Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of MSCs or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage fluid and tissues were collected for analyses. Longer-term studies were performed with antibiotic coadministration to assess the effect of MSCs on survival. MEASUREMENTS AND MAIN RESULTS: MSC treatment significantly reduced mortality in septic mice receiving appropriate antimicrobial therapy. MSCs alone reduced systemic and pulmonary cytokine levels in mice with CLP-induced sepsis, preventing acute lung injury and organ dysfunction, despite the low levels of cell persistence. Microarray data highlighted an overall down-regulation of inflammation and inflammation-related genes (such as IL-10, IL-6) and a shift toward up-regulation of genes involved in promoting phagocytosis and bacterial killing. Finally, bacterial clearance was significantly greater in MSC-treated mice, in part due to enhanced phagocytotic activity of the host immune cells. CONCLUSIONS: These data demonstrate that MSCs have beneficial effects on experimental sepsis, possibly by paracrine mechanisms, and suggest that immunomodulatory cell therapy may be an effective adjunctive treatment to reduce sepsis-related morbidity and mortality. |
DOI | 10.1164/rccm.201001-0010OC |
Alternate Journal | Am. J. Respir. Crit. Care Med. |
PubMed ID | 20558630 |